Sakati Syndrome

Synonyms of Sakati Syndrome

ACPS III

ACPS with Leg Hypoplasia

Acrocephalopolysyndactyly Type III

Sakati-Nyhan Syndrome

General Discussion

Sakati syndrome is an extremely rare disorder that belongs to a group of rare genetic disorders known as "Acrocephalopolysyndactyly" (ACPS). All forms of ACPS are characterized by premature closure of the fibrous joints (cranial sutures) between certain bones of the skull (craniosynostosis), causing the top of the head to appear pointed (acrocephaly); webbing or fusion (syndactyly) of certain fingers or toes (digits); and/or more than the normal number of digits (polydactyly). In addition, Sakati syndrome, which is also known as ACPS type III, is associated with abnormalities of bones of the legs, structural heart malformations that are present at birth (congenital heart defects), and/or other findings. Sakati syndrome is thought to be caused by a new genetic change (mutation) that occurs randomly for unknown reasons (sporadically). This mutation is inherited as an autosomal dominant trait.

Signs & Symptoms

In Sakati syndrome, the fibrous joints between the bones in the skull (cranial sutures) close prematurely (craniosynostosis), causing an affected infant’s head to grow upward at an accelerated rate. As a result, the head appears long, narrow, and pointed at the top (acrocephaly). Affected individuals also have several unusual facial characteristics including a flat, abnormally small face; protruding eyes; an abnormally wide space between the eyes (ocular hypertelorism); an elongated nose; large, malformed (dysplastic) and low-set ears; and a prominent forehead.

Sakati syndrome is also characterized by several deformities of the hands and feet, including abnormally short fingers (brachydactyly), unusually broad thumbs and big toes, webbed toes (syndactyly), and more than the normal number of fingers and/or toes (polydactyly). Abnormalities of the legs are also present, including bowed thigh bones (femurs); abnormally shaped, displaced calf bones (fibulas); and underdeveloped shin bones (hypoplastic tibias). In addition, both the legs and arms are shorter than normal.

Additional symptoms associated with this disorder may include teeth that are crowded together, an underdeveloped upper jaw bone (maxillary hypoplasia), jaws that project forward (prognathism), a short neck, a low hairline, absence of hair (alopecia), and congenital heart disease. Intelligence is usually within normal limits.

Causes

The exact cause of Sakati syndrome is not fully understood. It is believed that the syndrome may be caused by a new or sporadic, dominant genetic change (mutation). Although the exact reason for such a mutation remains unclear, some researchers suggest that advanced parental age may be a contributing factor.

If a person with Sakati syndrome were to have children, the altered gene for the disorder may be transmitted as an autosomal dominant trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

Affected Populations

Sakati syndrome is named after the researcher (N. Sakati) who, along with colleagues, originally described the condition in 1971. They reported the disease entity in a single male child of a couple who were of advanced parental age. This apparently remains the only case reported in the medical literature to date.

Related Disorders

Symptoms of the following disorders can be similar to those of Sakati syndrome. Comparisons may be useful for a differential diagnosis:

Acrocephalopolysyndactyly (ACPS) is a group of very rare genetic disorders including Noack syndrome (Type I), Carpenter syndrome (Type II), Sakati syndrome (Type III), and Goodman syndrome (Type IV). All of these disorders are characterized by a long, narrow head that appears pointed at the top (acrocephaly), more than the usual number of fingers and/or toes (polydactyly), and webbing of fingers and/or toes (syndactyly).

Carpenter syndrome (Acrocephalopolysyndactyly Type II) is a very rare inherited disorder characterized by a long, narrow head (acrocephaly); abnormally short, webbed fingers (brachysyndactyly); and feet with more than five toes that may also be webbed (polysyndactyly). Affected individuals have characteristic downslanted eyes, a flattened nasal bridge, broad cheeks, low-set ears, and underdeveloped jaw bones (hypoplastic mandible). Other features may include mild obesity, mental retardation, protrusion of portions of the intestines through the abdominal wall (abdominal hernias), underdeveloped sex organs (hypogenitalism), and congenital heart disease. Carpenter syndrome is inherited as an autosomal recessive trait. (For more information on this disorder, choose “Carpenter” as your search term in the Rare Disease Database.)

Goodman syndrome (Acrocephalopolysyndactyly Type IV) is an extremely rare genetic disorder characterized by a long, narrow head (acrocephaly); several facial defects; webbed fingers and/or toes (syndactyly); extra fingers (postaxial polydactyly); and fifth fingers that are abnormally bent (clinodactyly) and permanently flexed (camptodactyly). Other features include a deviation of one of the forearm bones (ulna), abnormally close together knees and abnormally far apart ankles (genu valgum), and congenital heart disease. Intelligence is within normal limits. Some researchers feel that Goodman syndrome is a variant of Carpenter syndrome (Acrocephalopolysyndactyly Type II), which is described above. Goodman syndrome is inherited as an autosomal recessive trait. (For more information on this disorder, choose “Goodman” as your search term in the Rare Disease Database.)

Apert syndrome (Acrocephalosyndactyly Type I) is a rare genetic disorder characterized by a wedge-shaped or pointed head; a prominent forehead; a face that may appear flat in the middle; and eyes that may protrude, appear to squint, and/or be set widely apart (ocular hypertelorism). Abnormalities of the hands and feet may include fingers and toes that are webbed and/or fused (syndactyly) and a single nail that is common to the second to fourth fingers. Other features may include crowded upper teeth, a prominent jaw (mandible), an unusually high and pointed palate (gothic palata), low-set ears, hearing loss, and mental retardation. It is believed that Apert syndrome is inherited as an autosomal dominant trait. (For more information on this disorder, choose “Apert” as your search term in the Rare Disease Database.)

Diagnosis

Sakati syndrome can be detected at birth, based upon a clinical evaluation and identification of characteristic physical findings.

Standard Therapies

Treatment

Treatment primarily consists of surgical correction of malformations. Early craniofacial surgery may be performed to correct the premature closure of the bones in the skull (craniosynostosis) and. Additional craniofacial surgery may be done later in life as well as surgery to correct deformities of the hands and feet. In addition, surgical repair of the bone abnormalities of the legs may also be performed to improve the affected individuals' ability to walk.

Infants with Sakati syndrome who have congenital heart defects may also be treated surgically. The surgical procedure performed will depend upon the severity and location of the heart defects and their associated symptoms.

Other treatment is symptomatic and supportive. Genetic counseling will be of benefit for affected individuals and their families.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

Years Published

1994, 2001, 2008

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